Medicine and Health Sciences Commons^™

Mechanism Of Catch Force: Tethering Of Thick And Thin Filaments By Twitchin., Thomas M Butler, Marion J Siegman

Department of Molecular Physiology and Biophysics Faculty Papers

Catch is a mechanical state occurring in some invertebrate smooth muscles characterized by high force maintenance and resistance to stretch during extremely slow relaxation. During catch, intracellular calcium is near basal concentration and myosin crossbridge cyctng rate is extremely slow. Catch force is relaxed by a protein kinase A-mediated phosphorylation of sites near the N- and C- temini of the minititin twitchin (approximately 526 kDa). Some catch force maintenance car also occur together with cycling myosin crossbridges at submaximal calcium concentrations, but not when the muscle is maximally activated. Additionally, the link responsible for catch can adjust during shortening of …

Diverticular And Aneurysmal Structures Of The Left Ventricle In Adults: Report Of A Case Within The Context Of A Literature Review., Premraj Makkuni, Morris N Kotler, Vincent M. Figueredo

Department of Medical Genetics Faculty Papers

Left ventricular outpouchings are increasingly detected on cardiovascular imaging. Herein, we describe the case of a 45-year-old man who underwent noncardiac preoperative imaging and was found to have an asymptomatic left ventricular outpouching. The patient underwent successful surgical repair of the structure. When left ventricular outpouchings are detected, the main differential diagnoses are pseudoaneurysm, aneurysm, and diverticulum. The outcomes for these conditions differ substantially, and accurate diagnosis can be crucial in making clinical decisions. We review the relevant medical literature, outline the natural history of these left ventricular abnormalities, and discuss options in regard to their management.

Jefferson Review - Winter 2010

Jefferson Review

Content

Features

• 4 - A Capital Idea: Jefferson Community Takes a Stand
• 8 - Burn Camp Crosses Border into Israel
• 20 - OTD Grads Find Approach Meaningful

On Campus

• 12 - School of Health Professions
• 14 - School of Nursing
• 16 - School of Pharmacy
• 17 - School of Population Health
• 22 - Class Notes
• 24 - Commencement 2009

The Role Of Chemotherapy In The Management Of Newly Diagnosed Brain Metastases: A Systematic Review And Evidence-Based Clinical Practice Guideline., Minesh P Mehta, Nina A Paleologos, Tom Mikkelsen, Paula D Robinson, Mario Ammirati, David W Andrews, Anthony L Asher, Stuart H Burri, Charles S Cobbs, Laurie E Gaspar, Douglas Kondziolka, Mark E Linskey, Jay S Loeffler, Michael Mcdermott, Jeffrey J Olson, Roy A Patchell, Timothy C Ryken, Steven N Kalkanis

Department of Neurosurgery Faculty Papers

TARGET POPULATION: This recommendation applies to adults with newly diagnosed brain metastases; however, the recommendation below does not apply to the exquisitely chemosensitive tumors, such as germinomas metastatic to the brain.

RECOMMENDATION: Should patients with brain metastases receive chemotherapy in addition to whole brain radiotherapy (WBRT)? Level 1 Routine use of chemotherapy following WBRT for brain metastases has not been shown to increase survival and is not recommended. Four class I studies examined the role of carboplatin, chloroethylnitrosoureas, tegafur and temozolomide, and all resulted in no survival benefit. Two caveats are provided in order to allow the treating physician to …

Interaction Of The Mu-Opioid Receptor With Gpr177 (Wntless) Inhibits Wnt Secretion: Potential Implications For Opioid Dependence., Jay Jin, Saranya Kittanakom, Victoria Wong, Beverly A S Reyes, Elisabeth J Van Bockstaele, Igor Stagljar, Wade Berrettini, Robert Levenson

Department of Neurosurgery Faculty Papers

BACKGROUND: Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs) may help to elucidate the underlying mechanisms involved in the development of opioid dependence. RESULTS: GPR177, the mammalian ortholog of Drosophila …

Molecular Staging Estimates Occult Tumor Burden In Colorectal Cancer, Alex Mejia, Stephanie Schulz, Terry Hyslop, David S. Weinberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumor cells in regional lymph nodes are a key prognostic marker of survival and predictive marker of response to adjuvant chemotherapy in colorectal cancer. However, clinicopathologic techniques to detect lymph node metastases remain imperfect, and ~30% of patients with lymph nodes negative by histology (pN0) develop recurrent disease, reflecting occult metastases that escape detection. These observations underscore an unmet clinical need for accurate approaches to identify occult nodal metastases in colorectal cancer patients. GUCY2C is a receptor whose expression normally is restricted to intestinal epithelial cells, but is universally over-expressed by colorectal cancer cells. A prospective, multicenter, blinded clinical trial …

Selection Of Optimal Reference Genes For Normalization In Quantitative Rt-Pcr., Inna Chervoneva, Yanyan Li, Stephanie Schulz, Sean Croker, Chantell Wilson, Scott A Waldman, Terry Hyslop

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Normalization in real-time qRT-PCR is necessary to compensate for experimental variation. A popular normalization strategy employs reference gene(s), which may introduce additional variability into normalized expression levels due to innate variation (between tissues, individuals, etc). To minimize this innate variability, multiple reference genes are used. Current methods of selecting reference genes make an assumption of independence in their innate variation. This assumption is not always justified, which may lead to selecting a suboptimal set of reference genes. RESULTS: We propose a robust approach for selecting optimal subset(s) of reference genes with the smallest variance of the corresponding normalizing factors. …

Expression Of The Intestinal Biomarkers Guanylyl Cyclase C And Cdx2 In Poorly Differentiated Colorectal Carcinomas., Brody Winn, Rosemarie Tavares, Andres Matoso, Lelia Noble, Jacqueline Fanion, Scott A Waldman, Murray B Resnick

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylyl cyclase C, a receptor for bacterial diarrheagenic enterotoxins, is expressed selectively by intestinal epithelium and is an endogenous downstream target of CDX2. The expression of Guanylyl cyclase C is preserved throughout the adenoma/carcinoma sequence in the colorectum. Detection of Guanylyl cyclase C expression by reverse transcriptase-polymerase chain reaction is currently being validated as a technique to identify occult lymph node metastases in patients with colorectal cancer and for circulating cells in the blood for postoperative surveillance. Although Guanylyl cyclase C is widely expressed by well-differentiated colorectal cancer, its expression in poorly differentiated colorectal cancer has not been evaluated. A …

Innovative Approaches To Generational Instruction: Welcoming The Nexters Via The Hybrid, Kellie Smith, Rn, Msn, Kathleen Clark, Rn, Msn, Cnrn, Apn, Bc

College of Nursing Faculty Papers & Presentations

Students currently entering higher
education were born between 1980-
2000 and are often referred to as
NeXters, Millennials, or Generation Y.

An undergraduate nursing core
curriculum course was developed and
implemented using a constructivist
pedagogy approach which
characterizes generational
distinctiveness to optimize learning
and student satisfaction.

Ionizing Radiation, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

In Remembrance Of Denis Alan Trevor New, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Does Diabetes Mellitus Influence Pathologic Complete Response And Tumor Downstaging After Neoadjuvant Chemoradiation For Esophageal And Gastroesophageal Cancer? A Two-Institution Report., Shayna L. Showalter, Ernest L. Rosato, P Rani Anne, Walter Scott, Edith Mitchell, Adam C. Berger

Department of Surgery Faculty Papers

BACKGROUND: Esophageal carcinoma is an aggressive disease that is often treated with neoadjuvant therapy followed by surgical resection. Diabetes mellitus (DM) has been associated with reduced efficacy of chemoradiation (CRT) in other gastrointestinal cancers. The goal of this study was to determine if DM affects response to neoadjuvant CRT in the management of gastroesophageal carcinoma.

METHODS: We retrospectively reviewed the esophageal cancer patient databases and subsequently analyzed those patients who received neoadjuvant CRT followed by surgical resection at two institutions, Thomas Jefferson University (TJUH) and Fox Chase Cancer Center (FCCC). Comparative analyses of rates of pathologic complete response rate (pCR) …

Sustained Expression Of Tdp-43 And Fus In Motor Neurons In Rodent's Lifetime., Cao Huang, Pedro Yuxing Xia, Hongxia Zhou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS) are two highly conserved ribonucleoproteins. Pathogenic mutations of the TDP-43 or the FUS gene are all linked to amyotrophic lateral sclerosis (ALS) that is characterized by progressive degeneration of motor neurons. To better understand the correlation of ALS disease genes with the selectivity of chronic motor neuron degeneration, we examined the longitudinal expression of the TDP-43 and the FUS genes in C57BL6 mice and in Sprague-Dawley rats. TDP-43 and FUS were robustly and ubiquitously expressed in the postnatal mice and rats, but were markedly decreased in the adult rodents. In adulthood, …

Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS), which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of …

Imaging Spontaneous Mmtvneu Transgenic Murine Mammary Tumors: Targeting Metabolic Activity Versus Genetic Products., Mathew L Thakur, Devakumar Devadhas, Kaijun Zhang, Richard G Pestell, Chenguang Wang, Peter Mccue, Eric Wickstrom

Department of Radiology Faculty Papers

INTRODUCTION: Despite the great strides made in imaging breast cancer (BC) in humans, the current imaging modalities miss up to 30% of BC, do not distinguish malignant lesions from benign ones, and require histologic examinations for which invasive biopsy must be performed. Annually in the United States, approximately 5.6 million biopsies find benign lesions. More than 50% of human BCs overexpress cyclin D1, and all BCs exhibit VPAC1 oncogene products. Together, these gene products may provide an excellent biomarker for the early and accurate detection of BC. We have evaluated 4 biologically active peptide analogs that have high affinity for …

Differential Gene Expression Profile Of Retinoblastoma Compared To Normal Retina., Arupa Ganguly, Carol L Shields

Wills Eye Hospital Papers

PURPOSE: The retinoblastoma gene (RB1) is a tumor suppressor gene that was first discovered in a rare ocular pediatric tumor called retinoblastoma (RB). The RB1 gene is essential for normal progression through the cell cycle and exerts part of its function through the family of transcription factors (E2F) and many other intermediaries. In the absence of normal RB1, genomic instability and chromosomal aberrations accumulate, leading to tumor initiation, progression, and ultimately metastasis. The purpose of this report was to identify the molecular pathways that are deregulated in retinoblastoma.

METHODS: We compared gene expression signatures of matched normal retinal tissue and …

Effect Of Visual Media Use On School Performance: A Prospective Study, Iman Sharif, Md, Mph, Thomas A. Wills, Phd, James D. Sargent, Md

Department of Pediatrics Faculty Papers

Purpose: To identify mechanisms for the impact of visual media use on adolescents' school performance.

Methods: We conducted a 24-month, four-wave longitudinal telephone study of a national sample of 6,486 youth aged 10 to 14 years. Exposure measures: latent construct for screen exposure time (weekday time spent viewing television/playing videogames, presence of television in bedroom) and variables for movie content (proportion of PG-13 and R movies viewed).

Outcome measure: self- and parent reports of grades in school. Effects of media exposures on change in school performance between baseline and 24 months were assessed using structural equation modeling. Information about hypothesized …

Reduced Mortality And Increased Bpd With Histological Chorioamnionitis And Leukocytosis In Very-Low-Birth-Weight Infants., David A. Paul, Md, Kelly Zook, Md, Amy Mackley, Rnc, Robert G. Locke, Do

Department of Pediatrics Faculty Papers

OBJECTIVE: To investigate the association between leukocytosis, mortality and bronchopulmonary dysplasia (BPD) in very-low-birth-weight infants (VLBW) born to mothers with histological chorioamnionitis.

STUDY DESIGN: A retrospective cohort study from a single level 3 neonatal intensive care unit. The study sample included infants born to mothers with histological chorioamnionitis (n=252). Total white blood cells (WBCs) after birth were measured. Leukocytosis was defined as a total WBC count >30 000 per mm(3) in the first 2 days of life. Outcomes investigated included BPD and death. Both unadjusted and multivariable analyses were carried out.

RESULT: After controlling for potential confounding variables, infants who …

Jefferson Alumni Bulletin – Volume 59, Number 1, Winter 2010

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 59, Number 1, Winter 2010

Dean's Message, page 2

Findings: Study Targets Scourge of U.S. Military, page 4

The Rewards and Challenges of Translational Medicine: The Patient-Centered Medical Home, page 6

Beyond the Office Visit: Jefferson Focuses on Advocacy, page 12

Eakins Scholar Follows Her Own Path, page 16

Jefferson Faculty Compile First Medical Professionalism Textbook, page 18

Faculty Profile: Karen Knudsen: Piecing Together the Prostate Cancer Puzzle, page 20

On Campus, page 22

Class Notes, page 28

In Memoriam, page 34

By the Numbers, page 37

Superficial Dsg2 Expression Limits Epidermal Blister Formation Mediated By Pemphigus Foliaceus Antibodies And Exfoliative Toxins., D Brennan, Ying Hu, Walid Medhat, A Dowling, M G Mahoney

Department of Dermatology and Cutaneous Biology Faculty Papers

Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF) and staphylococcal scalded skin syndrome (SSSS) are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1). To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg) mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT) mice were injected with purified ETA or PF Ig. …

The Most Important Medical Source: Aunt Mabel Knows Best., Lawrence Parish, Joseph A Witkowski

Department of Dermatology and Cutaneous Biology Faculty Papers

Not so long ago, one of us was consulted by a middle-aged woman with rosacea. For many years, she had had periodic flares of red papules and pustules on her nose and the adjoining areas. The confluent telangiectasia on her cheeks gave a permanent appearance of well-applied rouge. She had seen several dermatologists and had received a wide variety of medications, all of which seemed appropriate except to her as would be subsequently revealed. She wanted a new approach, but there were limitations placed upon her request: no pills or capsules; nothing odiferous; no agent that might bleach clothing; and …

Early Detection Of Response To Hydroxyurea Therapy In Patients With Sickle Cell Anemia., Samir K. Ballas, William F. Mccarthy, Nan Guo, Carlo Brugnara, Gail Kling, Robert L. Bauserman, Myron A. Waclawiw

Department of Medicine Faculty Papers

Red blood cells (RBC) and reticulocyte parameters were determined on peripheral blood from a subset of patients enrolled in the multicenter study of hydroxyuea (HU) in sickle cell anemia. Multiple blood samples were obtained every 2 weeks. Cellular indices were measured by flow cytometry. Generalized linear models were used to determine the relationship between the longitudinal trajectories of RBC and reticulocyte indices and HU usage. There was a significant relationship between HU usage and most of the RBC and reticulocyte indices. Hydroxyurea produced higher value trajectories than those generated by placebo usage for the hemoglobin (Hb) content of both the …

Mast Cells And Hypoxia Drive Tissue Metaplasia And Heterotopic Ossification In Idiopathic Arthrofibrosis After Total Knee Arthroplasty., Theresa A Freeman, Javad Parvizi, Craig J Dela Valle, Marla J Steinbeck

Department of Orthopaedic Surgery Faculty Papers

ABSTRACT: BACKGROUND: Idiopathic arthrofibrosis occurs in 3-4% of patients who undergo total knee arthroplasty (TKA). However, little is known about the cellular or molecular changes involved in the onset or progression of this condition. To classify the histomorphologic changes and evaluate potential contributing factors, periarticular tissues from the knees of patients with arthrofibrosis were analyzed for fibroblast and mast cell proliferation, heterotopic ossification, cellular apoptosis, hypoxia and oxidative stress. RESULTS: The arthrofibrotic tissue was composed of dense fibroblastic regions, with limited vascularity along the outer edges. Within the fibrotic regions, elevated numbers of chymase/fibroblast growth factor (FGF)-expressing mast cells were …

Biological Impact Of Geometric Uncertainties: What Margin Is Needed For Intra-Hepatic Tumors?, Hsiang-Chi Kuo, Wen-Shan Liu, Andrew Wu, Dennis Mah, Keh-Shih Chuang, Linda Hong, Ravi Yaparpalvi, Chandan Guha, Shalom Kalnicki

Department of Radiologic Sciences Faculty Papers

BACKGROUND: To evaluate and compare the biological impact on different proposed margin recipes for the same geometric uncertainties for intra-hepatic tumors with different tumor cell types or clinical stages. METHOD: Three different margin recipes based on tumor motion were applied to sixteen IMRT plans with a total of twenty two intra-hepatic tumors. One recipe used the full amplitude of motion measured from patients to generate margins. A second used 70% of the full amplitude of motion, while the third had no margin for motion. The biological effects of geometric uncertainty in these three situations were evaluated with Equivalent Uniform Doses …

Fdg-Pet Staging And Importance Of Lymph Node Suv In Head And Neck Cancer., Gregory J Kubicek, Collin Champ, Shannon Fogh, Fen Wang, Eashwer Reddy, Charles Intenzo, Reginald W Dusing, Mitchell Machtay

Department of Radiation Oncology Faculty Papers

OBJECTIVES: The role of positron emission tomography (PET) with fluoro-deoxy-glucose (FDG) in the staging of head and neck cancer (HNC) is unclear. The NCCN guidelines do not recommend FDG-PET as a part of standard workup. The purpose of this report is to examine the role of FDG-PET imaging in altering management and providing prognostic information for HNC.

METHODS: Retrospective review of HNC patients who had a staging FDG-PET scan performed at either Thomas Jefferson University or University of Kansas Medical Center between the years 2001 and 2007. A total of 212 PET scans were performed in patients who went on …

Definitions Of The Phenotypic Manifestations Of Sickle Cell Disease., Samir K Ballas, Susan Lieff, Lennette J Benjamin, Carlton D Dampier, Matthew M Heeney, Carolyn Hoppe, Cage S Johnson, Zora R Rogers, Kim Smith-Whitley, Winfred C Wang, Marilyn J Telen

Department of Medicine Faculty Papers

Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD ( approximately 100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of …

The Development And Implementation Of A Curriculum Using Simulation To Teach Interns Basic Invasive Clinical Skills, C. Sultana, K. Berg, J. Kairys, J. Majdan, M. Vergare, D. Berg

Department of Obstetrics and Gynecology Faculty Papers

The ACGME requires that all residents are competent in performing basic invasive clinical procedures. Although simulation models have been used in other programs to teach these skills to interns with the intent to provide training and skills attainment before learning and performing on real patients, a large scale, mandatory simulation training, in which every incoming intern must satisfactorily complete training in a simulation center, prior to starting their intern year, has yet to be described. We describe such a curricular intervention produced in our Simulation Center.

A Novel Curriculum Using Simulation To Teach And Assess Indications And Technique Of Handwashing To Gme Learners, K. Berg, C. Sultana, R. Sorokin, J. Kairys, M. Vergare, D. Berg

Department of Obstetrics and Gynecology Faculty Papers

Proficiency in the clinical skill of effective hand washing is integral to high quality health care. Studies at our hospital revealed that in 2008, of 1215 direct, anonymous, observations of residents and attendings, only 53.3% washed their hands correctly during clinical activities. Medical students in fiscal year 2009 (July 1, 2008-June 30 2009) had a 52% compliance rate from 109 observations. This data prompted our hospital to work with the faculty of the University Clinical Skills and Simulation Center (UCSSC) to develop a module on the indications and technique of effective handwashing. This intervention, using multimedia simulation was introduced to …

The Role Of Surgical Resection In The Management Of Newly Diagnosed Brain Metastases: A Systematic Review And Evidence-Based Clinical Practice Guideline., Steven N Kalkanis, Douglas Kondziolka, Laurie E Gaspar, Stuart H Burri, Anthony L Asher, Charles S Cobbs, Mario Ammirati, Paula D Robinson, David W Andrews, Jay S Loeffler, Michael Mcdermott, Minesh P Mehta, Tom Mikkelsen, Jeffrey J Olson, Nina A Paleologos, Roy A Patchell, Timothy C Ryken, Mark E Linskey

Department of Neurosurgery Faculty Papers

QUESTION: Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings? Target population These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection. Recommendations Surgical resection plus WBRT versus surgical resection alone Level 1 Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone. Surgical resection plus WBRT versus SRS +/- …

The Role Of Stereotactic Radiosurgery In The Management Of Patients With Newly Diagnosed Brain Metastases: A Systematic Review And Evidence-Based Clinical Practice Guideline., Mark E Linskey, David W Andrews, Anthony L Asher, Stuart H Burri, Douglas Kondziolka, Paula D Robinson, Mario Ammirati, Charles S Cobbs, Laurie E Gaspar, Jay S Loeffler, Michael Mcdermott, Minesh P Mehta, Tom Mikkelsen, Jeffrey J Olson, Nina A Paleologos, Roy A Patchell, Timothy C Ryken, Steven N Kalkanis

Department of Neurosurgery Faculty Papers

QUESTION: Should patients with newly-diagnosed metastatic brain tumors undergo stereotactic radiosurgery (SRS) compared with other treatment modalities? Target population These recommendations apply to adults with newly diagnosed solid brain metastases amenable to SRS; lesions amenable to SRS are typically defined as measuring less than 3 cm in maximum diameter and producing minimal (less than 1 cm of midline shift) mass effect. Recommendations SRS plus WBRT vs. WBRT alone Level 1 Single-dose SRS along with WBRT leads to significantly longer patient survival compared with WBRT alone for patients with single metastatic brain tumors who have a KPS > or = 70.Level 1 …